Effect of aromatic isothiocyanates on the functional properties of human hemoglobin. Role of the stereochemistry of the charged group.
The effect of chemical modification of hemoglobin with six derivatives of benzene isothiocyanate has been studied. The negatively charged reagents (isothiocyanates of benzoic and benzenesulfonic acids) markedly inhibit the interaction of hemoglobin with allosteric effectors such as H+, Cl- and organic phosphates; the affinity for heme ligands in the absence of effectors is reduced but cooperativity is maintained, making these modified hemoglobins suitable models for a possible 'blood substitute'. The only uncharged reagent tested (isothiocyanate of benzenesulfonamide) increases the oxygen affinity of hemoglobin and affects only slightly the interaction with heterotropic ligands; its potential use as an antisickling drug is under study.
Ippoliti
R
R
Dipartimento di Scienze Biochimiche, Università La Sapienza, Roma, Italy.
Currell
D
D
Lendaro
E
E
Bellelli
A
A
Castagnola
M
M
Bolognesi
M
M
Brunori
M
M
D001555:Benzene Derivatives / Q000494:pharmacology*; D001665:Binding Sites; D002712:Chlorides / Q000378:metabolism / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D046911:Macromolecular Substances; D010108:Oxyhemoglobins / Q000378:metabolism*; D010446:Peptide Fragments / Q000302:isolation & purification; D013861:Thiocyanates / Q000494:pharmacology*; D014357:Trypsin
D001555:Benzene Derivatives; D002712:Chlorides; D006454:Hemoglobins; D046911:Macromolecular Substances; D010108:Oxyhemoglobins; D010446:Peptide Fragments; D013861:Thiocyanates; D014357:Trypsin